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However, over 50% of patients experience limited or no response to ICI therapy. Resistance to ICIs is influenced by a complex interplay of tumour intrinsic and extrinsic factors. This review summarizes current ICIs for melanoma and the factors involved in resistance to the treatment. We also discuss emerging evidence that the microbiota can impact ICI treatment outcomes by modulating tumour biology and anti-tumour immune function. Furthermore, microbiota profiles may offer a non-invasive method for predicting ICI response. Therefore, future research into microbiota manipulation could provide cost-effective strategies to enhance ICI efficacy and improve outcomes for melanoma patients.<\/jats:p>","DOI":"10.3390\/ijms251810120","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T10:49:48Z","timestamp":1726829388000},"page":"10120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Immune Checkpoint Inhibitor Therapy for Metastatic Melanoma: What Should We Focus on to Improve the Clinical Outcomes?"],"prefix":"10.3390","volume":"25","author":[{"given":"Sultana Mehbuba","family":"Hossain","sequence":"first","affiliation":[{"name":"Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Ly","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yih Jian","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antony","family":"Braithwaite","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S227","DOI":"10.33549\/physiolres.934757","article-title":"Inhibitory immune checkpoint molecules and exhaustion of T cells in COVID-19","volume":"70","author":"Barnova","year":"2021","journal-title":"Physiol. 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